The control of cell proliferation is of great interest both for its fundamental biological importance and for its relevance to the problem of cancer. The simple, unicellular eukaryote Saccharomyces cerevisiae (yeast) offers exceptional advantages for experimental studies of many aspects of the control of cell proliferation (Hartwell (1974) Bacteriol. Rev. 38, 164). Foremost among these advantages is the ease with which genetic analysis of the cell division cycle can be conducted. Previous genetic and physiological studies have led to the hypothesis (Hartwell et al. (1974) Science 184, 46) that the overall control of cell proliferation in yeast is exerted at an event (named "start") in G1 at the very beginning of the cell cycle. "Start" can be completed (and a cell division cycle thus initiated) only when certain conditions (including adequate supplies of nutrients, attainment of a critical cell size, and absence of mating pheromone) are met. This model is compatible with many data obtained with other types of cells. It is now proposed to continue the analysis of "start" by isolating and characterizing additional mutants that display abnormal control of the "start" event. Several promising isolation schemes are available. It should be possible to isolate conditional (temperature-sensitive) mutants that are unable to complete the "start" event, mutants that complete the "start" event (thus initiating cell cycles) at inappropriate times, and mutants that complete the "start" event at an atypical cell size. Analysis of the properties of these mutants should provide information necessary for the development of plausible, testable hypotheses as to the molecular mechanisms involved in the control of cell proliferation.